The purpose of the project is to determine the incidence rates, rates of progression, and risk factors for the chronic complications of NIDDM. The study is conducted in the Pima Indians of the Gila River Indian Community, who have participated in a longitudinal epidemiologic study since 1965 (see project Z01 DK 69000). Risk factors for the major complications of diabetes, retinopathy, nephropathy, coronary artery disease, and peripheral vascular disease are determined by longitudinal followup of diabetic subjects. Methods of ascertainment of these complications include fundus photography, measurement of urine albumin and serum creatinine concentrations, electrocardiography, and documentation of lower extremity amputations. Some determinants of diabetic nephropathy precede the development of diabetes. An albumin-to-creatinine ratio (A/C) was measured in 237 nondiabetic Pima Indians without clinical proteinuria who developed diabetes at least one year later. After the onset of diabetes, the prevalence of an elevated A/C was directly related to the prediabetic A/C. To determine if parental blood pressure was also associated with proteinuria in subjects with diabetes, the blood pressure was measured in both parents of 438 diabetic Pima Indians. The prevalence of proteinuria in the diabetic subjects if neither parent had hypertension was similar to that if one parent had hypertension, but was significantly higher if both parents had hypertension. This relationship remained when controlled for hypertension in the diabetic subjects. Thus, prediabetic albuminuria and parental hypertension were risk factors for abnormal albumin excretion once a subject developed diabetes. Medial arterial calcification (MAC) of the feet is another common complication of NIDDM, and its relationship with mortality was examined in 1363 diabetic Pima Indians. MAC was associated with mortality from all causes and from diabetic nephropathy. In an assessment of whether there was an effect on mortality which was in addition to that of proteinuria, either MAC or proteinuria alone was associated with a significant increase in risk and both MAC and proteinuria together conferred and even higher risk.